Spatial immune niche remodeling of the neutrophil-macrophage axis inchronic liver disease

Chronic liver disease (CLD) arises from diverse etiologies, featuring persistent inflammation, progressive fibrosis and eventual hepatocellular carcinoma (HCC). Dynamic remodeling of the hepatic immune microenvironment dominates CLD progression. As core innate immune cells, neutrophils and macrophages form a critical crosstalk hub linking inflammatory response and tissue remodeling. The 2 cell populations interact bidirectionally via direct cell contact and soluble mediators including cytokines, chemokines, extracellular vesicles and neutrophil extracellular traps (NETs), building a complicated regulatory network. This network mediates hepatic stellate cell activation, fibrotic progression and tumor immune escape as sterile inflammation exacerbates. Mechanistically, neutrophil-derived NETs and reactive oxygen species (ROS) trigger macrophage nuclear factor-κB (NF-κB) and NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signaling. Macrophages reciprocally secrete chemokines to recruit neutrophils and modulate their functional phenotypes. Notably, this crosstalk exhibits stage-dependent effects: it amplifies inflammation at early disease phases yet drives immunosuppression and tissue remodeling at late stages. This review systematically addresses neutrophil and macrophage phenotypic heterogeneity and their interactive mechanisms in CLD, highlighting stage-specific spatiotemporal functional reprogramming and summarizing targeted therapeutic strategies. Elucidating this core immune axis lays novel theoretical foundations and therapeutic targets for precision immune intervention against CLD.